iloprost and Hyperemia

We evaluated the effectiveness of intravenous iloprost (IVI) in outpatients with thromboangiitis obliterans (TAO) and lower limb noninvasive transcutaneous monitoring (TCM) at follow-up (FU). Ten consecutive patients with TAO underwent IVI therapy. Transcutaneous oxygen (TcPo 2) and carbon dioxide (TcPco 2) determination and laser Doppler flowmetry (LDF) were performed before and after IVI at 3, 6, and 12 months of FU. Clinical response was positive in 7 patients, whereas 3 nonresponders underwent a second IVI cycle with 1 showing a late positive clinical response. After 12 months of FU, all patients were alive without amputations. Supine and dependent TcP2 levels significantly improved (P < .005). Hallux LDF values showed significant change with the maximal hyperemic test at 44°C (P < .005). Forefoot maximal hyperemic test at 44°C LDF (P < .005) and improved venous arterial reflex (P < .05) showed statistically significant time evolution. We demonstrated some degree of IVI effectiveness and evaluated TCM in patients with TAO.

Topics: Adult; Blood Flow Velocity; Blood Gas Monitoring, Transcutaneous; Female; Humans; Hyperemia; Iloprost; Laser-Doppler Flowmetry; Lower Extremity; Male; Microcirculation; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Predictive Value of Tests; Recovery of Function; Regional Blood Flow; Thromboangiitis Obliterans; Time Factors; Treatment Outcome; Vasodilator Agents; Young Adult

The physiological basis of postischemic hyperemia is not yet fully understood. The present study investigated the effects of pharmacologic manipulation of the prostaglandin system on local hemodynamics. Strain-gauge plethysmography was used to study 8 normal subjects and 9 patients with obliterating arterial disease of the lower limbs. Hemodynamic evaluations were performed before treatment, after seven days of low-dose acetylsalicylic acid (100 mg/day) to inhibit platelet thromboxane synthesis, and after acute infusion of 1 g of acetylsalicylic acid to inhibit endothelial prostacyclin synthesis. In patients with arterial disease, the hemodynamic study was also carried out after infusion of iloprost, a synthetic prostacyclin analogue. Acute infusion of acetylsalicylic acid significantly reduced basal blood flow in normal subjects, but not in patients with arterial disease. In the latter group, iloprost affected neither basal nor maximal postischemic flow. The study also evaluated the role of endothelin in musculocutaneous hemodynamic regulation, both in physiological conditions and in atherosclerosis. This part of the study addressed the possibility that the hemodynamic effects of vasodilator prostanoids like prostacyclin might affect endothelin release in vivo. During reactive hyperemia, plasma endothelin was reduced in normal subjects (-1.02 pg/mL, 95% CI: -2.23, 0.08), but not in patients with atherosclerosis (-0.35 pg/mL, 95% CI: -1.45, 0.75). In both groups, plasma endothelin was not affected by aspirin. These findings confirm the role of prostacyclin in local hemodynamic regulation. In the normal subject, musculocutaneous blood flow seems to depend at least in part on the action of vasodilator prostanoids and endothelin. This is not the case in patients with arterial disease, in whom plasma endothelin does not seem to be affected by postischemic changes in blood flow. A possible explanation for this difference could be alteration of the endothelial function in patients with arterial disease, related to the functional and structural characteristics of the artery wall in atherosclerosis.

Topics: Aged; Arteriosclerosis; Aspirin; Endothelins; Epoprostenol; Hemodynamics; Humans; Hyperemia; Iloprost; Ischemia; Leg; Middle Aged; Platelet Aggregation Inhibitors; Plethysmography; Regional Blood Flow; Vasodilator Agents

One and 2 micrograms of prostaglandin F2 alpha isopropyl ester (PGF2 alpha -IE) applied topically to the rabbit eye caused a biphasic response. The hypotensive phase was dose-dependent with a maximum reduction in intraocular pressure (IOP) of 9.4 +/- 1.7 mmHg at a dose of 2 micrograms. In beagles, 0.4 to 2 micrograms topical PGF2 alpha-IE resulted in a sustained IOP reduction; 2 micrograms produced the maximum reduction of 7-9 mmHg. No initial hypertensive response was observed. Iloprost phenacyl ester (Iloprost-PE) caused a greater decrease in IOP when dissolved in 0.5% hydroxypropyl methylcellulose (AT) than in saline. In rabbits, doses of 0.1 to 1 microgram in AT caused a biphasic response with a sustained IOP decrease fluctuating between 7 and 8 mmHg. In beagles 1 and 2 micrograms Iloprost-PE resulted in a mean IOP reduction of 5.8 +/- 0.4 mmHg and 5.8 +/- 0.5 mmHg (P less than 0.005), respectively; the decrease persisted for 5 hrs. No initial hypertensive response was observed. In beagles PGF2 alpha-IE induced a strong miosis lasting more than 6 hours; Iloprost-PE had no effect on pupil size. Both PG-esters induced a slight hyperemia in rabbit and beagle eyes. In rabbits Iloprost-PE affects the blood-aqueous barrier more than PGF2 alpha-IE, since higher protein concentrations are seen in the aqueous humor after application of Iloprost-PE. Neither PG-ester had a noticeable effect on aqueous protein in beagles. In rabbits, both PG-esters led to slightly increased aqueous humor cyclic-AMP concentrations. In beagles aqueous humor cyclic-AMP was elevated only after Iloprost-PE.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Animals; Aqueous Humor; Cyclic AMP; Dinoprost; Dogs; Dose-Response Relationship, Drug; Epoprostenol; Hyperemia; Hypromellose Derivatives; Iloprost; Intraocular Pressure; Methylcellulose; Pupil; Rabbits; Time Factors; Tonometry, Ocular

Topical application of Iloprost caused a dose-dependent decrease in intraocular pressure (IOP) in rabbits and ocular hypertensive beagles. In rabbits, the IOP response was biphasic and miosis was observed. In beagles, there was no initial hypertensive phase, and the fall in IOP was more pronounced (up to 37%). In beagles, Iloprost did not influence pupillary diameter. A mild transient hyperemia was noted in both rabbit and beagle eyes. Iloprost led to an increase in the aqueous humor protein concentration in rabbits but not in beagles. The use of artificial tears as vehicle enhanced the effect on intraocular pressure but also aqueous protein in rabbits. The central corneal temperature was increased after application of Iloprost in both rabbits and beagles. In rabbits, tonography revealed an increase in outflow facility during both the hypertensive and the hypotensive phases. Iloprost caused a decrease in mean arterial pressure in beagles; the effect on pulse rate was inconsequential. It is suggested that similar low doses of an analog of Iloprost or carboprostacyclin that does not affect the hemodynamic equilibrium could be of value in the treatment of glaucoma.

Topics: Animals; Aqueous Humor; Ascorbic Acid; Blood Pressure; Body Temperature; Conjunctiva; Cornea; Dogs; Dose-Response Relationship, Drug; Epoprostenol; Eye Proteins; Heart Rate; Hyperemia; Iloprost; Intraocular Pressure; Ocular Hypertension; Pupil; Rabbits